The cell population kinetics of tumors have been studied to provide a rational basis for design of therapeutic protocols but kinetic data that ignores a fraction of the tumor cell population may be very misleading. Kinetic studies, from this laboratory, using tritiated thymidine techniques for a spectrum of experimental tumors indicate that the observed thymidine index and the shape of the percent labeled mitoses curve are functions of the duration of emulsion exposure and are also tumor-dependent. Specifically, the distribution of tritiated thymidine incorporated per cell in a tumor population is a function of the tumor system and the experimental condition often fail to detect a variable fraction of the "lightly" labeled cells at the lower end of the distribution. The biological or biochemical mechanisms responsible for the labeling characteristics of the tumor and the population kinetics of these "lightly" labeled cells may be related to the response of the tumor system to chemotherapy. We propose to utilize a spectrum of experimental tumors that exhibit a range of sensitivities to chemotherapy (1) to study the biological or biochemical mechanisms responsible for the observed distributions of incorporated tritiated thymidine, (2) to determine the relationship of the "lightly" labeled cells to chemotherapeutic response, (3) to investigate means of exploiting the relationship for improvement of protocol design and, (4) to establish objective criteria for evaluation of the existing body of kinetic data and for future kinetic studies.